Genital Herpesvirus hominis (HVH) constitutes the second or third most common sexually transmitted disease in the United States. Its high recurrence rate, complications of meningitis, radiculitis, neonatal morbidity, and its association with cervical cancer make studies of the epidemiology, pathogenesis and therapy of HVH of broad interest. We propose to test our current hypotheses concerning HVH of broad interest. We propose to test our current hypotheses concerning HVH latency and recurrence in humans and as a secondary objective further prospectively describe the clinical epidemiology of genital HVH. Among patients with primary genital HVH only 30 percent subsequently recrudesced contrasted with 60 percent recrudescence in HVH-2 patients. We plan to recruit and follow additional primary disease patients to expand our data base and to determine the effects of covariables also associated with recrudescence, race, age, sexual behavior, and cell mediated immunity. We have also seen that only 10 percent of primary HVH-1 patients had detectable anti-HVH antibody compared to 93 percent of primary HVH-2 patients. We wish to see if preexisting anti-HVH antibody protects against type 1 or 2 clinical disease and to examine other variables which may interact to influence this. We know that asymptomatic HVH infection occurs and may precede clinical recrudescence. By weekly culturing of couples who suffer recurrent episodes we can evaluate the relative frequency of asymptomatic vs. symptomatic genital recurrences in men and women. Lastly we plan to test the hypothesis that recurrent genital herpes depends upon a mechanism of antigenic drift. We will look for subtle antigenic differences using serial isolates from individual patients, serial sera from patients and rabbit anti-HVH raised against specific serial isolates.